R. Seidenfaden et H. Hildebrandt, Retinoic acid-induced changes in polysialyltransferase mRNA expression andNCAM polysialylation in human neuroblastoma cells, J NEUROBIOL, 46(1), 2001, pp. 11-28
Polysialic acid (PSA) is a dynamically regulated carbohydrate modification
of the neural cell adhesion molecule NCAM, which is implicated in neural di
fferentiation and cellular plasticity. The cloning and characterization of
two polysialyltransferases, termed ST8SiaII (STX) and ST8SiaIV (PST), opene
d up new perspectives in the search for factors that control this unique ce
ll surface glycosylation. In vitro and transfection approaches revealed tha
t ST8SiaII and ST8SiaIV are independently capable of synthesizing PSA on NC
AM with slightly different specificities towards the major NCAM isoforms an
d glycosylation sites. Their overlapping but distinct expression patterns d
uring brain development point towards an independent transcriptional regula
tion. However, the factors driving their joint or distinct expression, as w
ell as the significance of divergent expression patterns in vivo, are not y
et understood. In the present study, the mRNA expression of ST8SiaII and ST
8SiaIV was comparatively analyzed in neuronal differentiation of PSA-positi
ve human neuroblastoma cell lines induced by retinoic acid (RA), phorbolest
er, or growth factors. Using a semiquantitative RT-PCR strategy, we demonst
rated a general decrease in the mRNA level of ST8SiaII upon differentiation
of SH-SY5Y and LAN-5 cells. In contrast, a drastic increase of ST8SiaIV wa
s specifically induced by RA-treatment of SH-SY5Y cells. To explore the sig
nificance of these changes, the cellular capacity to perform PSA synthesis
and the degree of NCAM polysialylation were analyzed. Our data indicate tha
t the increased expression of ST8SiaIV enables an accelerated polysialylati
on of NCAM, which, however, is not converted into higher amounts of PSA. (C
) 2000 John Wiley & Sons, Inc.